PALBOCICLIB + PD-0325901 for NSCLC & Solid Tumors
KRAS Mutant Non-Small Cell Lung Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the MEK Inhibitor PD-0325901 for Patients With KRAS Mutant Non-Small Cell Lung Cancer and Other Solid Tumors|
- Safety and tolerability [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]Toxicities will be graded using version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE).
- Maximum Tolerated Dose and Recommended Phase 2 Dose [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]A standard 3+3 design will be implemented to discover the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of study drugs. A dose will be declared the MTD if zero or 1 patient out of 6 experience a dose limiting toxicity (DLT) at the highest dose level below the maximally administered dose. This is generally the RP2D.
- Pharmacokinetics [ Time Frame: 2 Years ] [ Designated as safety issue: No ]The pharmacokinetic properties for the combination of palbociclib and PD-0325901 will be evaluated utilizing serial blood draws on cycle 1 day 1 and a steady state trough level drawn on cycle 1 day 15.
- Target engagement of palbociclib and PD-0325901 [ Time Frame: 2 Years ] [ Designated as safety issue: No ]Confirm target engagement of palbociclib and PD-0325901 in pre- and on-treatment tumor biopsies from patients enrolled to an MTD expansion cohort.
- Overall Response Rate [ Time Frame: 2 Years ] [ Designated as safety issue: No ]Evaluate the preliminary clinical efficacy of palbociclib and PD-0325901 in advanced solid tumors using CT and MRI scans per RECIST version 1.
|Study Start Date:||January 2014|
|Estimated Study Completion Date:||December 2020|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Experimental: Palbociclib and PD-0325901
Palbociclib will be administered orally once daily, 3 weeks out of every 4 in each cycle. The initial dose for phase 1 of the study will be 75 mg daily. Dosing will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. No pre-medications for palbociclib are required. It should be administered without food with patients fasting for 1 hour prior and 2 hours post drug administration.
Other Name: PD 0332991-00Drug: PD-0325901
PD-0325901 will be administered orally twice daily, 3 weeks out of every 4 in each cycle. The initial dose for phase 1 of the study will be 2 mg twice daily. Dosing will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. PD-0325901 will be administered using a flat-dosing plan. No premedications are required. As the effect of food on PD-0325901 is uncertain, patients will be permitted to dose either fasting or after food.
This will be an open label Phase I/II dose escalation study evaluating the combination of the CDK4/6 inhibitor palbociclib (PD-0332991) and the MEK inhibitor PD-0325901. To determine the maximally tolerated dose (MTD) and recommended phase 2 dose (RP2D), a 3+3 dose escalation protocol will be undertaken. Once the RP2D has been determined, the study will then evaluate, in a randomized phase II study design, the combination of palbociclib and PD-0325901 compared to PD-0325901 alone and palbociclib alone in KRAS mutant NSCLC.
- Phase 1: The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have cancer, not everyone who participates in this research study will receive the same dose of the study drug. The dose the participant receives will depend on the number of participants who have been enrolled in the study before and how well the dose has been tolerated.
- Study Drug(s): The participant will be given a study drug-dosing calendar for each treatment cycle. Each treatment cycle lasts 4 weeks during which time you will be taking the study drug for 3 weeks at a time. The participant will take Palbociclib by mouth once a day, every day for 3 weeks. The participant will take PD-0325901 by mouth twice a day, every day for 3 weeks.
- Clinical Exams: During all cycles the participant will have a physical exam and will be asked questions about general health and specific questions about any problems that they might be having and any medications they may be taking.
- Scans (or Imaging tests): The investigators will assess the participant's tumor by either a CT scan or MRI
- Blood Tests: These are special tests to check the amount of drug and the amount of tumor DNA in the participant's blood at specific points in time.
Phase II Outcomes:
- Determine the response rate, as determined by RECIST 1.1, of the combination of palbociclib and PD-0325901 to that of palbociclib or PD-0325901 as single agents in patients with advanced KRAS mutant NSCLC
- Further evaluate the safety, tolerability and side effect profile for the combination of palbociclib and PD-0325901 Phase II Secondary Outcomes
- Determine the rate of progression free survival ≥ 4 months and the median PFS for the combination of palbociclib and PD-0325901 compared to palbociclib or PD-0325901 as single agents in KRAS mutant NSCLC
Please refer to this study by its ClinicalTrials.gov identifier: NCT02022982
|Contact: Geoffrey Shapiro, MD, PhD||(617) 632-4942||GSHAPIRO@PARTNERS.ORG|
|United States, Massachusetts|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Andrew Wolanski, NP 617-632-6623 AWOLANSKI@PARTNERS.ORG|
|Principal Investigator: Geoffrey Shapiro, MD, Ph.D|
|Principal Investigator:||Geoffrey Shapiro, MD. Ph.D||Dana-Farber Cancer Institute|